In one aspect, this invention relates to a chemical purification process. In another aspect, the invention relates to a container for chemicals. In another aspect, the invention relates to a clean-up kit for use with radioisotopes prior to the manufacture of radiopharmiceutical products with such radioisotopes.
Indium-111 is a radioisotope which is used for radio-diagnostic and radio-therapeutic purposes. Indium-111 (atomic number 49) has a half-life of about 2.8 days and decays by emission of an electron to form cadmium-111 (atomic number 48). The short half-life is beneficial from the standpoint of quickly breaking down when administered to a patient, but is problematic from the standpoint of requiring extremely prompt (and careful) handling of the material between the producer of the radioisotope and the patient. Delays between the time of production of the material its incorporation into a pharmaceutical material, and its administration to a patient result in a decrease in the amount of Indium-111, with a resultant decrease in radioactive potency (curies/volume), and a concomitant increase in the concentration of the cadmium decay product (mass/volume).
Indium-111 is typically received for the preparation of a radiopharmaceutical in a small glass vial which contains a specific dose of Indium-111 chloride in hydrochloric (HCl) acid solution. The dose is typically measured by the radioactive output of the vial, typically in millicuries. The radioactive output is typically a calculated value for a specific time and day. In order to deliver the calculated dose to a target site, it is necessary to transfer all of the Indium-111 in the vial to the target site at the indicated time.
Delivery is typically accomplished by incorporating the Indium-111 into a radiopharmaceutical product. This is typically done by reacting the Indium-111 with an organic moiety, such as a peptide, which will seek the target site when introduced into the patient. The stoichiometries of the reactions between the Indium-111 and the organic moiety, and the radiopharmaceutical and the target site, however, is complicated by the presence of the cadmium, and may be further complicated by the presence of further impurities commonly found in Indium-111 solution, such as iron, lead, zinc, aluminum and copper.
The cadmium competes with the Indium-111 for reaction with the organic moiety, and the cadmium-pharmaceutical competes with the Indium-111 radiopharmaceutical for binding with the target site. Stoichiometry is also complicated by the fact that a significant portion of the indium-111 cannot be easily removed from the vial. Apparently, a portion of the indium can become chemically bound to the glass. Further, the amount of cadmium which is present can be greater than the amount calculated as being present from the decay of the Indium-111 . Apparently, cadmium, as well as other impurities which are inherent to the glass, can be leached out by the solution from the inside of the glass vial.
The glass wall of the vial causes a further complication in delivering a prescribed radioactive dose to the target site. The actual output of the radioactive material in the vial is often different from the measured radioactive output from the vial, due to attenuation or radioactive shielding by the glass wall of the vial, and can be as much as 30% higher.
Simple techniques for removing the cadmium from the Indium-111 solution and for getting all of the Indium-111 from the vial would be very desirable, as this would enable higher quantities of ultra-pure Indium-111 to be delivered to the target site.
Techniques for providing ultra-pure Indium-111 to the end user, and for enabling the end user to better assess the potency of the dose of Indium-111 to be administered would also be desirable.